Method for providing support during vaccinations and during adaptive immune system response

ABSTRACT

The present invention provides formulations and methods for formulation administration that support an individual&#39;s body during vaccination and adaptive immune response. The individuals who can benefit from these formulations and methods for formulation administration are infants, children and adults. The formulations comprise ingredients that may be administered prior to, concurrent with or subsequent to the vaccination. The formulations and methods for formulation administration of the present invention preferably act by selectively targeting enzymatic reactions, epigenetic expression, and an individual&#39;s various metabolic pathways in support of immune system homeostasis, maintaining balance between oxidative stress and methylation, fostering balance between Th1 and Th2 responses, or a combination thereof, during vaccination and adaptive immune responses to improve vaccine response and reduce vaccine side effects.

CROSS-REFERENCE TO RELATED APPLICATION

This nonprovisional application claims benefit of provisionalapplication U.S. Ser. No. 62/200,446 filed Aug. 3, 2015, provisionalapplication U.S. Ser. No. 62/345,227 filed Jun. 30, 2016, nonprovisionalapplication Ser. No. 15/226,415 filed Aug. 2, 2016, and nonprovisionalapplication U.S. Ser. No. 16/280,356 filed Feb. 20, 2019.

FEDERAL FUNDING LEGEND

This invention was not created using federal funds.

BACKGROUND OF THE INVENTION Field of the Invention

The present invention generally relates to formulations that providesupport to an individual's body during vaccinations and adaptive immuneand methods thereof. More specifically, the present invention is drawnto formulations that comprise novel combinations of ingredients thattarget epigenetic regulation of gene expression, specific enzymaticreactions, cytokine differentiation and immune system homeostasis invarious metabolic pathways in an individual during vaccination andadaptive immune system response. The administration of the formulationmay improve antibody response and decrease vaccine side effects toprovide and safer and more effective vaccinations for the population atlarge by improving the synthesis and release of cellular biomarkers.

Background

The mitochondrion is known to function as the powerhouse of the cellbecause it produces the energy that an individual's body requires tosurvive. However, in this process of energy production, it producesreactive oxygen species that are harmful to the body. Glutathione is aprimary antioxidant that protects the body from the harmful effects ofreactive oxygen species such as free radicals, heavy metals andperoxides. Glutathione is a tripeptide made up of three amino acids(glutamate, glycine and cysteine). Cysteine, which is the rate limitingfactor in glutathione synthesis can either be made in the cell by aprocess called transulfuration or can be obtained from outside the cell,for instance, from diet or through nutrient support.

Glutathione exists in two forms, including reduced glutathione (GSH) andthe non-reactive, oxidized form (glutathione disulfide form; GSSG)depending on the amount of electrons it carries. Glutathione is in areactive state when it is reduced (GSH) and in a non-reactive state whenit is oxidized (GSSG). Reduced glutathione (GSH) gives up an electron,and thus becomes reactive, but then readily bonds with another oxidativeglutathione molecule to form non-reactive glutathione disulfide (GSSG).GSSG is a disulfide formed from the bonding of two oxidative glutathionemolecules. The bonding neutralizes the two oxidative glutathionemolecules. Due to the rapid nature of the reduction of the oxidized formof glutathione relative to its synthesis or secretion, the ratio ofreduced glutathione to oxidized glutathione is a good indicator of theoxidative stress within cells.

Oxidative stress is important for reasons including but not limited toits ability to inhibit methylation. However, methylation is veryessential as it is involved in the single carbon transfer of molecules.Defects in single carbon transfer are associated with many differentdiseases and cellular dysfunction. One of the most essential methylationreactions involves DNA, histone and specific CpG island methylation,which has implications with regard to gene expression, cytokinedifferentiation and immune regulation. Methylation is also involved incertain enzymatic pathways and bodily functions that include but are notlimited to creatine and adenosine synthesis (energy production),phospholipid synthesis (cellular membrane integrity), serotonin andmelatonin production, biopterin (BH4) synthesis (amino acid metabolism),glutathione synthesis, arginine metabolism (nitrous oxide synthesis),catecholamine production (cognitive status), and CpG island methylationfor adequate production of interferon gamma for immune systemhomeostasis. Thus, disruption of methylation equilibrium plays acritical role in global disease states and may play a role in vaccineresponse.

Conventional methods and formulations lack the ability to beneficiallytarget gene expression for proper enzymatic reactions involved inmetabolic pathways, in vaccine response and in adaptive immune responseincluding but not limited to those involved in maintaining the delicatebalance between methylation, transsulfuration, and oxidative stress forhealthy cellular metabolism. Further, there is a current lack of focuson the mechanisms that cause individuals to respond or not respond tostandard vaccine protocols. Thus, there is a long-felt but significantand un-met need in the art for formulations and methods that canbeneficially target such enzymatic reactions, and help essentiallymaintain the delicate balance between methylation, transsulfuration, andoxidative stress—or a combination thereof to improve vaccine responseand reduce vaccine side effects. Still further, there is a long-felt andsignificant but un-met need in the art of supportive immunizationprotocols that can target epigenetic expression, enzymatic kinetics andimmune system homeostasis to improve vaccine response and reduce sideeffects. The present invention satisfies this long standing need in theart.

SUMMARY OF EMBODIMENTS OF THE INVENTION

In a preferred embodiment, the present invention is directed to aformulation, comprising: thiamine (Vitamin B1), a derivative thereof oran analog thereof; riboflavin (Vitamin B2), a derivative thereof or ananalog thereof, niacin (Vitamin B3), a derivative thereof or an analogthereof; pantothenic acid (Vitamin B5), a derivative thereof or ananalog thereof; Vitamin B6, a derivative thereof or an analog thereof;folate (Vitamin B9), a derivative thereof or an analog thereof;cobalamin (Vitamin B12), a derivative thereof or an analog thereof;Vitamin A, a derivative thereof or an analog thereof; Vitamin D, aderivative thereof or an analog thereof; Vitamin E, a derivative thereofor an analog thereof, Vitamin C, a derivative thereof or an analogthereof; Vitamin K, a derivative thereof or an analog thereof; calcium,a derivative thereof or an analog thereof; iodine, a derivative thereofor an analog thereof: magnesium, a derivative thereof or an analogthereof; zinc, a derivative thereof or an analog thereof; selenium, aderivative thereof or an analog thereof; manganese, a derivative thereofor an analog thereof; chromium, a derivative thereof or an analogthereof; molybdenum, a derivative thereof or an analog thereof;trimethylglycine (betaine), a derivative thereof or an analog thereof;choline, a derivative thereof or an analog thereof; acetyl-L-carnitine,a derivative thereof or an analog thereof; N-acetyl cysteine, aderivative thereof or an analog thereof; milk thistle (Silybum marianum,preferably at least 80% silymarin), a derivative thereof or an analogthereof; creatinine, a derivative thereof or an analog thereof; or acombination thereof.

In another embodiment, the ingredients in the formulation are in thepure form, substantially pure form or synthetic form.

In yet another embodiment, the formulation comprises about 0.1 mg-10 mg,preferably about 0.5 mg of thiamin, about 0.1 mg-500 mg, preferablyabout 5 mg of riboflavin, about 0.5 mg-1 g, preferably about 5 mg ofniacin, about 0.5 mg-10 mg, preferably about 2 mg of pantothenic acid,about 0.1 mg-25 mg, preferably about 2 mg of Vitamin B6, about 5 mcg-1mg, preferably about 100 mcg of folate, about 10 mcg-5,000 mcg,preferably about 50 mcg of cobalamin, about 10 mcg-1,000 mcg, preferablyabout 100 mcg of Vitamin A, about 50 IU-1,000 IU, preferably about 400IU of Vitamin D, about 1 mg-20 mg, preferably about 5 mg of Vitamin E,about 5 mg-5,000 mg, preferably about 50 mg of Vitamin C, about 0.5mcg-300 mcg, preferably about 2.5 mcg of Vitamin K, about 50 mg-800 mg,preferably about 200 mg of calcium, about 20 mcg-15 mg, preferably about130 mcg iodine, about 5 mg-200 mg, preferably about 75 mg of magnesium,about 1 mg-15 mg, preferably about 2.5 mg of zinc, about 5 mcg-200 mcg,preferably about 25 mcg of selenium, about 0.1 mg-5 mg, preferably about0.6 mg of manganese, about 1 mcg-150 mcg, preferably about 10 mcg ofchromium, about 1 mcg-100 mcg, preferably about 20 mcg of molybdenum,about 100 mg-5 g, preferably about 500 mg of trimethylglycine (betaine),about 10 mg-1 g, preferably about 20 mg of choline, about 50 mg-2 g,preferably about 200 mg of acetyl-L-carnitine, about 20 mg-500 mg,preferably about 100 mg of N-acetyl cysteine, about 50 mg-800 mg,preferably about 200 mg of milk thistle (Silybum marianum, 80%silymarin), about 20 mg-800 mg, preferably about 100 mg of creatinine ora combination thereof.

In still yet another embodiment, the formulation further comprises apharmaceutically acceptable carrier, an excipient or a combinationthereof.

In further yet another embodiment, the excipient includes but is notlimited to a flavoring agent, a coloring agent, a stabilizing agent, abinder, or a disintegrant.

In yet another embodiment, the formulation has beneficial effects onimmune system, detoxification, cell membrane integrity,s-adenosylmethionine (SAM) production, DNA synthesis and repair,glutathione production, nervous system or a combination thereof.

In still yet another embodiment, the formulation maintains balance orsubstantially maintains balance between oxidative stress andmethylation, maintains balance between Th1 and Th2 response, targetsspecific enzymatic reactions in metabolic pathways, targets epigeneticregulation of gene expression, targets cytokine differentiation, or acombination thereof.

In further yet another embodiment, the formulation targets enzymaticreactions in metabolic pathways comprising trans-methylation,trans-sulfuration, citric acid cycle, biopterin production, amino acidmetabolism, mitochondrial function, or a combination thereof.

In still further yet another embodiment, the formulation maintains thebalance between the Th1 and Th2 responses by regulating methylation ofspecific CpG islands, production of cytokines responsible formaintaining balance between Th1 and Th2 response, or both.

In yet another embodiment, the cytokine production is regulation byregulating production of IFN-γ, IL-4, IL-5, IL-13, IL-10, IL-25, IL-31,or IL-33.

In another preferred embodiment, the present invention is directed to amethod of supporting an individual's body during vaccination, duringadaptive immune response or both, comprising: administeringpharmacologically acceptable amount of the formulation described hereinto the individual.

In yet another embodiment, the formulation is administered prior to theadministration of the vaccine, concurrent with the administration of thevaccine or subsequent to the administration of the vaccine.

In still yet another embodiment, the formulation is administered orally,intramuscularly, intradermally, intravenously, nasally, subcutaneously,or intraperitoneally.

In further yet another embodiment, the administered formulationmaintains balance or substantially maintains balance between oxidativestress and methylation, maintains balance between Th1 and Th2 response,targets specific enzymatic reactions in metabolic pathways, targetsepigenetic regulation of gene expression, targets cytokinedifferentiation, or a combination thereof.

In still further yet another embodiment, the administered formulationtargets enzymatic reactions in metabolic pathways comprisingtrans-methylation, trans-sulfuration, citric acid cycle, biopterinproduction, amino acid metabolism, mitochondrial function, or acombination thereof.

In another embodiment, the administered formulation maintains thebalance between the Th1 and Th2 responses by regulating methylation ofspecific CpG islands, production of cytokines responsible formaintaining balance between Th1 and Th2 response, or both.

In yet another embodiment, the cytokine production is regulated byregulating production of IFN-γ, IL-4, IL-5, IL-13, IL-10, IL-25, IL-31,or IL-33.

In still yet another embodiment, the individual is an infant, a toddler,a teenager, or an adult.

DETAILED DESCRIPTION

The present invention discloses preferred formulations that beneficiallytarget certain enzymatic reactions in metabolic pathways, essentiallymaintain the balance between oxidative stress and methylation or both.The formulation described herein provides support to the bodies ofinfants, children and adults during vaccination. Additionally, theformulation also provides support to the individual's body duringadaptive immune response. It is contemplated herein that the formulationwill target epigenetic regulation of gene expression, specific enzymaticreactions, cytokine differentiation or a combination thereof in theindividual's body. It is also contemplated herein that the formulationwill play a role in maintaining proper balance between T helper 1 cell(Th1) and T helper 2 cell (Th2) responses. It is further contemplatedthe formulation maintains Th1 and Th2 responses by regulating mechanismsincluding but not limited to the methylation of specific CpG islands,production of cytokines responsible for maintaining the balance betweenTh1 and Th2 response, or both. Examples of the cytokines responsible formaintaining the balance of Th1 and Th2 response include but are notlimited to interferon gamma (IFN-γ), IL-4, IL-5, IL-13, IL-10 IL-25,IL-31, or IL-33. The metabolic pathways affected by the formulations ofthe present invention include, but are not limited to,trans-methylation, trans-sulfuration, citric acid cycle, biopterinproduction, amino acid metabolism and mitochondrial function. Theformulations of the present invention have further beneficial effects onvarious metabolic and biochemical reactions and systems including butnot limited to the immune system, detoxification, cell membraneintegrity, s-adenosylmethionine (SAM) production, DNA synthesis andrepair, glutathione production and beneficial effects on the nervoussystem.

Table 1 provides the ingredients in a representative, preferredformulation with the representative forms and representative dosages perserving.

TABLE 1 Representative Dosage Representative per serving PreferredDosage Ingredient Representative Form (range) per serving Thiamin (B1)Thiamine hydrochloride 0.1 mg-10 mg   0.5 mg Riboflavin (B2) Riboflavinand riboflavin- 0.1 mg-500 mg  5 mg 5-phosphate sodium Niacin (B3)Niacinamide 0.5 mg-1 g    5 mg Pantothenic acid (B5) D-calciumpantothenate 0.5 mg-10 mg   2 mg B6 Pyridoxal-5-phosphate and  0.1-25 mg2 mg pyridoxine HCl Folate (B9) L-5-MTHF (L-5- 5 mcg-1 mg  100 mcgmethyltetrahydrofolate) Cobalamin (B12) Methylcobalamin and   10mcg-5,000 mcg 50 mcg adenosylcobalamin Vitamin A Beta carotene andretinyl   10 mcg-1,000 mcg 100 mcg palmitate Vitamin D D3cholecalciferol   50 IU-1,000 IU 400 IU Vitamin E d-alpha tocopheryl 1mg-20 mg 5 mg succinate and mixed tocopherols Vitamin C Ascorbic acid  5 mg-5,000 mg 50 mg Vitamin K Menaquinone 0.5 mcg-300 mcg  2.5 mcgCalcium Calcium lactate 50 mg-800 mg 200 mg Iodine Iodine and iodide 20mcg-15 mg  130 mcg Magnesium Magnesium bis/glycinate  5 mg-200 mg 75 mgZinc Zinc citrate (40% 1 mg-15 mg 2.5 mg elemental) Selenium AA complex,chelate (L-  5 mcg-200 mcg 25 mcg selenomethionine) Manganese Manganese0.1 mg-5 mg   0.6 mg bisglycinate/chelate Chromium Nicotinate glycinate 1 mcg-150 mcg 10 mcg chelate Molybdenum Glycinate/chelate  1 mcg-100mcg 20 mcg Trimethylglycine Pure or substantially pure 100 mg-5 g    500mg (betaine) Choline Choline bitartrate 10 mg-1 g   20 mg L-carnitineAcetyl-L-carnitine 50 mg-2 g   200 mg N-acetyl cysteine Pure orsubstantially pure 20 mg-500 mg 100 mg Milk thistle (silybum Pure orsubstantially pure 50 mg-800 mg 200 mg mariamari) (80% silymarin)Creatine Pure or substantially pure 20 mg-800 mg 100 mg creatinemagnesium chelate

While Table 1 shows one example of the ingredients in a representative,preferred formulation with the representative forms and representativedosages per serving, the present invention broadly encompasses otherformulations that have variations in the types of ingredients, forms anddosages per serving. Each ingredient in the formulation plays a specificrole in providing support to an individual's body during vaccination andadaptive immune response. For instance, the B vitamins are involved inenergy metabolism with specific B vitamins targeted at methylation. Thecysteine in the formulation may be the rate limiting amino acid inglutathione production. The choline in the formulation is an integralcomponent to cellular membrane stability that is implicated severely byoxidative stress and methylation defects. The milk thistle (Silybummarianum) in the formulation may exert a hepatoprotective effect througha number of mechanisms including but not limited to antioxidantactivity, toxin blockade at the membrane level, enhanced proteinsynthesis, anti-inflammatory effect, or immunomodulating effect. This isimportant because the liver is one of the most metabolically activeorgans with over 2,500 mitochondria per hepatocyte and is the mainlocation for cellular metabolism, and maintaining equilibrium betweenmethylation, transsulfuration, and oxidative stress. The carnitine inthis formulation may act as an antioxidant and support the mitochondrialfunction through mechanisms including but not limited to fatty acidmetabolism and energy production. The trimethylglycine in thisformulation may act to support whole body methylation by providingmethyl donors, increasing S-adenosyl methionine levels and reducinghomocysteine levels. Trimethylglycine may also act as an osmolyte to aidin cellular hydration status. The creatine in this formulation may helpto support energy metabolism and lighten the majority demand ofmethyltransferase activity by providing the end product ofguanidinoacetate N-methyltransferase (GAMT). The other ingredients inthe formulation either support overall cellular physiology throughenergy production (enhancing mitochondrial function) or through theirwell-known antioxidant capabilities, thereby enhancing the delicatebalance between oxidative stress and methylation.

Each ingredient that is used in a formulation of the present inventionmay be used in a pure form, or a substantially pure form, as determinedby any suitable method for determination of purity that is well acceptedand established.

It is also to be understood that the inventors have contemplated thatany active isomer or metabolite of any ingredient listed in Table 1, orany combination thereof, may also be used in a formulation of thepresent invention.

In one embodiment, the present invention provides a formulationcomprising a combination of ingredients to support the body of anindividual during vaccination, adaptive immune response, or both,wherein the formulation acts by targeting specific enzymatic reactionsin metabolic pathways, target epigenetic regulation of gene expression,target cytokine differentiation, maintain balance or substantiallymaintain balance between oxidative stress and methylation, maintainproper balance between Th 1 and Th2 responses, or a combination thereof.In another embodiment, the formulation maintains balance between Th1 andTh2 responses by regulating mechanisms including but not limited to themethylation of specific CpG islands, production of cytokines responsiblefor maintaining balance between Th1 and Th2 response, or both. In yetanother embodiment, the cytokine production regulated by the formulationincludes but is not limited to the production of IFN-γ, IL-4, IL-5,IL-13, IL-10, IL-25, IL-31, or IL-33. In further yet another embodiment,the formulations targets enzymatic reactions involved in metabolicpathways including but not limited to trans-methylation,trans-sulfuration, citric acid cycle, biopterin production, amino acidmetabolism and mitochondrial function.

In another embodiment, the formulation comprises thiamin (Vitamin B1),riboflavin (Vitamin B2), niacin (Vitamin B3), pantothenic acid (VitaminB5), Vitamin B6, folate (Vitamin B9), cobalamin (Vitamin B12), VitaminA, Vitamin D, Vitamin E, Vitamin C, Vitamin K, calcium, iodine,magnesium, zinc, selenium, manganese, chromium, molybdenum,trimethylglycine (betaine), choline, acetyl-L-carnitine, N-acetylcysteine, milk thistle (Silybum marianum, 80% silymarin), creatinine ora combination thereof.

In certain embodiments, a formulation of the present invention mayinclude thiamine or a derivative of thiamine including but not limitedto thiamine hydrochloride, an analog of thiamine or a combinationthereof. The formulation may also include, for instance, thiaminemononitrate or thiamine nitrate.

In certain embodiments, a formulation of the present invention mayinclude riboflavin or a derivative of riboflavin including but notlimited to riboflavin-5-phosphate sodium, an analog of riboflavin or acombination thereof.

In certain embodiments, a formulation of the present invention mayinclude niacin or a derivative of niacin including but not limited toniacinamide, an analog of niacin or a combination thereof. Any suitableform of niacin may be used such as, for example, nicotinic acid(pyridine-3-carboxylic acid), nicotinamide (nicotinic acid amide), andother derivatives (e.g., inositol hexanicotinate) that exhibit thebiological activity of nicotinamide.

In certain embodiments, a formulation of the present invention mayinclude pantothenic acid or a derivative of pantothenic acid includingbut not limited to D-calcium pantothenate, an analog of pantothenic acidor a combination thereof.

In certain embodiments, a formulation of the present invention mayinclude a B6 or a derivative of B6 including but not limited topyridoxal-5-phosphate, pyridoxine HCl, an analog of B6 or a combinationthereof.

In certain embodiments, a formulation of the present invention mayinclude folate or a derivative of folate including but not limited toL-5-methyltetrahhydrofolate (L-5-MTHF), an analog of folate or acombination thereof. L-methylfolate calcium, metafolin, or levomefolicacid may also be used.

In certain embodiments, a formulation of the present invention mayinclude cobalamin or a derivative of cobalamin including but not limitedto methylcobalamin, adenosylcobalamin, hydroxycobalamin, an analog ofcobalamin or a combination thereof.

In certain embodiments, a formulation of the present invention mayinclude vitamin A or a derivative of vitamin A including but not limitedto beta carotene and retinyl palmitate, an analog of vitamin A or acombination thereof.

In certain embodiments, a formulation of the present invention mayinclude vitamin D or a derivative of vitamin D including but not limitedto D3 cholecalciferol, an analog of vitamin D or a combination thereof.

In certain embodiments, a formulation of the present invention mayinclude vitamin E or a derivative of vitamin E including but not limitedto d-alpha tocopherol, d-alpha tocopheryl acetate, d-alpha tocopherylsuccinate and mixed tocopherols, an analog of vitamin E or a combinationthereof.

The vitamin C in the formulation may, for example, be in the form ofascorbic acid. In certain embodiments, a formulation of the presentinvention may include a derivative of vitamin C including but notlimited to one or more salts of ascorbic acid, an analog of vitamin C ora combination thereof. Examples include, but are not limited to, calciumascorbate, sodium ascorbate, and other mineral ascorbates; ascorbic acidwith bioflavonoids; and combination products, such as Ester-C®, whichcontains calcium ascorbate, dehydroascorbate, calcium threonate,xylonate and lyxonate.

In certain embodiments, a formulation of the present invention mayinclude vitamin K or a derivative of vitamin K including but not limitedto menaquinone, an analog of vitamin K, isomer, or a combinationthereof.

In certain embodiments, a formulation of the present invention mayinclude calcium or a derivative of calcium including but not limited tocalcium lactate or other calcium salt, an analog or a combinationthereof. In certain embodiments of the invention, one or more variouscalcium salts may be used. Some representative salts of calcium include,for example, but not limited to, the acetate, lactobionate, carbonate,chloride, gluconate, and phosphate salts of calcium.

In certain embodiments, a formulation of the present invention mayinclude iodine or a derivative of iodine including but not limited toiodide, a salt form, an analog or a combination thereof. Representativeiodide salts that may be used include, but are not limited to, potassiumiodide, sodium iodide, and calcium iodide.

In certain embodiments, a formulation of the present invention mayinclude magnesium or a derivative of magnesium including but not limitedto magnesium bis/glycinate, other magnesium salt, an analog or acombination thereof. Other representative magnesium salts that may beused include, but are not limited to, magnesium chloride and magnesiumsulfate.

In certain embodiments, a formulation of the present invention mayinclude zinc or a derivative of zinc including but not limited to zinccitrate (for instance, 40% elemental), other zinc salt, an analog or acombination thereof. Other representative zinc salts that may be usedinclude, for example, zinc gluconate.

In certain embodiments, a formulation of the present invention mayinclude selenium or a derivative of selenium including but not limitedto AA complex and chelate (L-selenomethionine), an analog or acombination thereof.

In certain embodiments, a formulation of the present invention mayinclude manganese or a derivative of manganese including but not limitedto manganese bisglycinate/chelate, an analog, or a combination thereof.

In certain embodiments, a formulation of the present invention mayinclude chromium or a derivative of chromium including but not limitedto nicotinate glycinate chelate, an analog, or a combination thereof.

In certain embodiments, a formulation of the present invention mayinclude molybdenum or a derivative of molybdenum including, forinstance, glycinate/chelate, an analog, or a combination thereof.

In certain embodiments, a formulation of the present invention mayinclude trimethyglycine (betaine) or a derivative of betaine, an analogof betaine or a combination thereof. Representative forms that may beused include, for example, betaine anhydrous, betaine hydrochloride, andglycine betaine.

In certain embodiments, a formulation of the present invention mayinclude choline or a derivative of choline including but not limited tocholine bitartrate, an analog or a combination thereof.

In certain embodiments, a formulation of the present invention mayinclude carnitine or a derivative of carnitine including but not limitedto the biologically active enantiomer L-carnitine, acetyl-L-carnitine,glycine propionyl-L-carnitine (GPLC), an analog or a combinationthereof.

In certain embodiments, a formulation of the present invention mayinclude N-acetyl cysteine or a derivative of N-acetyl cysteine, ananalog of N-acetyl cysteine or a combination thereof.

In certain embodiments, a formulation of the present invention mayinclude milk thistle (Silybum marianum) or a derivative of milk thistle,an analog of milk thistle or a combination thereof. It is understoodthat milk thistle (Silybum marianum) has other accepted and establishednames including, for example, Cardus marianus, milk thistle, blessedmilk thistle, Marian thistle, Marythistle, Saint Mary's thistle,Mediterranean milk thistle, variegated thistle and Scotch thistle. Thespecies of Silybum marianum that is preferred is obtained from a plantof the Asteraceae family.

The creatine in the formulation may be a derivative of creatine, ananalog of creatine or a combination thereof. Representative forms ofcreatine include, for example, pure or substantially pure creatinemagnesium chelate, creatine Monohydrate, and creatine pyruvate. Othersuitable forms of creatine may also be used.

In another embodiment, the ingredients in the formulation may be in thepure, substantially pure or synthetic form. In yet another embodiment, arepresentative formulation comprises about 0.1 mg-10 mg, preferablyabout 0.5 mg of thiamin, about 0.1 mg-500 mg, preferably about 5 mg ofriboflavin, about 0.5 mg-1 g, preferably about 5 mg of niacin, about 0.5mg-10 mg, preferably about 2 mg of pantothenic acid, about 0.1 mg-25 mg,preferably about 2 mg of Vitamin B6, about 5 mcg-1 mg, preferably about100 mcg of folate, about 1 mcg-5,000 mcg, preferably about 50 mcg ofcobalamin, about 10 mcg-1,000 mcg, preferably about 100 mcg of VitaminA, about 50 IU-1,000 IU, preferably about 400 IU of Vitamin D, about 1mg-20 mg, preferably about 5 mg of Vitamin E, about 5 mg-5,000 mg,preferably about 50 mg of Vitamin C, about 0.5 mcg-300 mcg, preferablyabout 2.5 mcg of Vitamin K, about 50 mg-800 mg, preferably about 200 mgof calcium, about 20 mcg-15 mg, preferably about 130 mcg iodine, about 5mg-200 mg, preferably about 75 mg of magnesium, about 1 mg-15 mg,preferably about 2.5 mg of zinc, about 5 mcg-200 mcg, preferably about25 mcg of selenium, about 0.1 mg-5 mg, preferably about 0.6 mg ofmanganese, about 1 mcg-150 mcg, preferably about 10 mcg of chromium,about 1 mcg-100 mcg, preferably about 20 mcg of molybdenum, about 100mg-5 g, preferably about 500 mg of trimethylglycine (betaine), about 10mg-1 g, preferably about 20 mg of choline, about 50 mg-2 g, preferablyabout 200 mg of acetyl-L-carnitine, about 20 mg-500 mg, preferably about100 mg of N-acetyl cysteine, about 50 mg-800 mg, preferably about 200 mgof milk thistle (Silybum marianum, 80% silymarin), and about 20 mg-800mg, preferably about 100 mg of creatinine.

The formulations of the present invention preferably have furtherbeneficial effects on various metabolic and biochemical reactions andsystems including but not limited to the immune system, detoxification,cell membrane integrity, s-adenosylmethionine (SAM) production, DNAsynthesis and repair, glutathione production and the nervous system.

Moreover, the formulations of the present invention preferably maintainbalance, or substantially maintain balance between oxidative stress andmethylation, maintains balance between Th 1 and Th2 responses or both.

In certain embodiments, the formulations of the present invention may beadministered in a form including but not limited to capsules, tablets,syrups, liquids, and injectables. The formulations may be administeredusing any suitable dosage form. Moreover, the preparation of theformulations of the present invention is not limited to a specificmanufacturing process.

It is to be understood that the formulations of the present inventioncan also be prepared and administered with any pharmaceuticallyacceptable carrier or carriers. Moreover, a formulation of the presentinvention can also be prepared in such a manner that the formulationcomprises one or more pharmaceutically acceptable excipients. Examplesof some of the various classes or types of excipients that may be usedin preparation of the formulations include, but are not limited to,flavoring agents, coloring agents, stabilizing agents, binders,disintegrants, and other well-accepted types of excipients that are safeand effective for human use and consumption. Because it is wellunderstood that the number and type of specific excipients is tooexhaustive and numerous to be listed here, it is to be understood thatthe inventors of the present invention have contemplated that theformulations of the present invention may comprise any suitablecombination of one or more pharmaceutically acceptable excipients, forinstance, for preparation and manufacturing of the formulations. Suchrepresentative excipients that may be used for preparation of theformulations (for instance, for preparation of a suitable dosage formfor administration of a formulation) may include, but are not limitedto, one or more of the pharmaceutically acceptable excipients disclosedin the “Handbook of Pharmaceutical Excipients” (sixth edition, edited byRowe, Sheskey and Quinn), which is herein incorporated by reference.

In still yet another embodiment, the formulations of the presentinvention may be administered via routes including but not limited tooral, intramuscular, intradermal, intravenous, nasal, subcutaneous, orintraperitoneal. In further yet another embodiment, the formulation isadministered prior to, concurrent with or subsequent to the vaccination.

In another embodiment, the present invention provides a method tosupport an individual's body during vaccination. In yet anotherembodiment, the individual is an infant, a toddler, a teenager or anadult.

The formulation described herein can be administered to an individualand any suitable and well-established biochemical assay(s) can be usedfor accurate and reliable testing, analysis and measurement of thedisclosed and claimed biomarkers. The levels of these biomarkers can bemeasured at DNA, RNA and/or protein level using assays that are known inthe art. According to one preferred embodiment, one or more humanbiomarkers can be evaluated in vitro or ex vivo before and after theadministration of the formulation describe herein. For instance, samplesincluding but not limited to blood, serum, or plasma may be collected byany method known in the art prior to and/or after the administration ofthe formulation described herein to an individual by any of the meansdescribed herein or known in the art. A suitable, reliable, and accurateassay or assays can be used for accurate and reliable analysis andmeasurement of one or more biomarkers described herein, for instance,cytokines released by Th1 and Th2 cells. In accordance with the presentinvention, one representative approach/methodology that can be used forthe detection of biomarkers, e.g. from human serum is described in(“Highly Sensitive Diagnostic Assay for the Detection of ProteinBiomarkers Using Microresonators and Multifunctional Nanoparticles”, ACSNano, 2012, 6(5), pp 4375-4381.) Other representative analytical invitro and/or ex vivo methods or procedures for the detection of thebiomarkers described herein include but are not limited to intracellularcytokine staining, flow cytometry, Elispot assay, RNAse protectionassay, Northern blot, and ELISA.

In another preferred embodiment, the method of analyzing the degree orpercentage of methylation includes but is not limited to PolymeraseChain Reaction (PCR) or DNA sequencing.

The foregoing descriptions of the embodiments of the present inventionhave been presented for purposes of illustration and description. Theyare not intended to be exhaustive or to limit the present invention tothe precise forms disclosed. The exemplary embodiments were chosen anddescribed in order to best explain the principles of the presentinvention and its practical application, to thereby enable othersskilled in the art to best utilize the present invention.

What is claimed is:
 1. A method of supporting the healthy state of anindividual's body in conjunction with receipt of vaccinations and duringadaptive immune responses which target (1) epigenetic regulation of geneexpression, (2) specific enzymatic reactions, (3) cytokinedifferentiation, and (4) immune system homeostasis thereby improvingantibody response and decreasing vaccine side effects by positivelyaffecting the balance between oxidative stress, methylation,transsulfuration and maintaining the balance between Th1 and Th2response, comprising: administering a pharmacologically acceptableamount, to an individual, of the following formulation: 1 mg-10 mg ofthiamin (Vitamin B1), 0.1 mg-500 mg of riboflavin (Vitamin B2), 0.5 mg-1g of niacin (Vitamin B3), 0.5 mg-10 mg of pantothenic acid (Vitamin B5),0.1 mg-25 mg of pyridoxine (Vitamin B6), 5 mcg-1 mg of folate (vitaminB9), 10 mcg-5,000 mcg of cobalamin (Vitamin B12), 10 mcg-1,000 mcg ofVitamin A, 50 IU-1,000 IU of Vitamin D, 1 mg-20 mg of Vitamin E, 5mg-5,000 mg of Vitamin C, 0.5 mcg-300 mcg, of Vitamin K, 50 mg-800 mg ofCalcium, 20 mcg-15 mg of Iodine, 5 mg-200 mg of Magnesium, 1 mg-15 mg ofZinc, 5 mcg-200 mcg of Selenium, 0.1 mg-5 mg of Manganese, 1 mcg-150 mcgof chromium, 1 mcg-100 mcg of molybdenum, 10 mg-1 g of trimethylglycine(betaine), 10 mg-1 g of choline, 50 mg-2 g of acetyl-L-carnitine, 20mg-500 mg of N-acetyl cysteine, 50 mg-800 mg, of milk thistle and 20mg-800 mg of creatinine or a combination thereof; administering saidformulation prior to the administration of a vaccine, concurrent withthe administration of a vaccine or subsequent to the administration of avaccine; and administrating said formulation to said individual wherethe individual is an infant, a toddler, a teenager or an adult.
 2. Themethod of claim 1, wherein said administered formulation is administeredorally, intramuscularly, intradermally, intravenously, nasally,subcutaneously, intraperitoneally or any other suitable route ofadministration.
 3. The method of claim 1, wherein said administeredformulation is delivered via capsules, tablets, syrups, liquids,injectables or any suitable dosage forms.
 4. The method of claim 1,wherein said administered formulation further comprises: apharmaceutically acceptable carrier or carriers; and a pharmaceuticallyacceptable excipient or excipients including flavoring agents, coloringagents, stabilizing agents, binders, fillers, disintegrants, diluentsand/or other well-accepted types of excipients that are safe andeffective for human use and consumption.
 5. The method of claim 1,wherein said administered formulation beneficially targets metabolicpathways comprising trans-methylation, trans-sulfuration, the citricacid cycle, biopterin production, amino acid metabolism, mitochondrialfunction and/or a combination thereof.
 6. The method of claim 1, whereinadministration of said formulation maintains the balance between the Th1and Th2 responses by regulating methylation of specific CpG islands andby regulating the proper functioning of cytokines interferon gamma(IFN-γ), IL-4, IL-5, IL-13, IL-10, IL-25, IL-31, or IL-33.
 7. The methodof claim 1, wherein administration of said formulation has beneficialeffects on various metabolic and biochemical reactions and systemsincluding the immune system, cell membrane integrity, detoxification,s-adenosylmethionine (SAM) production, DNA synthesis and repair,glutathione production, and maintenance, support and maintenance of ahealthy nervous system.
 8. The method of claim 1, wherein theadministered formulation contains: B vitamins beneficially involved inenergy production and metabolism; cysteine essential for glutathioneproduction; choline integral to cellular membrane stability; milkthistle acting as hepatoprotective, an antioxidant, a toxin blocker, animmunomodulator, an anti-inflammatory and as an essential component forprotein synthesis; carnitine acting as an antioxidant and a support ofproper mitochondrial function through regulation of fatty acidmetabolism and energy production; trimethylglycine acting to hydratecells and to support methylation by providing reactive methyl donors,increasing S-adenosyl methionine levels and reducing homocysteinelevels; creatine to support energy metabolism and lighten the majoritydemand of methyltransferase activity by providing the end product ofguanidinoacetate N-methyltransferase (GAMT); and Vitamin A, Vitamin D,Vitamin E, Vitamin K, Calcium, Iodine, Magnesium, Zinc, Selenium,Manganese and Molybdenum for their roles as essential components to aproperly functioning, healthy individual undergoing vaccination and/oran adaptive immune response.
 9. The method of claim 1, wherein levels ofbiologic biomarkers may be collected and measured, via samples at theDNA, RNA and/or protein level, in vitro or ex vivo, before and after theadministration of said formulation, to provide accurate and reliabletesting, analysis and measurement to determine the effectiveness of saidformulation on immune system functioning and adaptive immune responses,specifically, and various metabolic and biochemical reactions andsystems, generally.
 10. The method of claim 1, wherein biologicbiomarkers may be measured and assessed through blood, serum or plasmasamples, before, during and after formulation administration, todetermine the effectiveness of said formulation on supporting anindividual's body during vaccination, an individual's immune systemfunction and adaptive immunity.